The purpose of this study is to define and clarify the enzymology of phagocytic superoxide (O2-) production. Based upon recent studies it is proposed that the NADPH dependent oxidoreductase associated with the plasmalemma of human PMN's is not a single enzyme, but a multienzyme complex, and that this multienzyme complex effects superoxide production through a series of linked redox reactions beginning with oxidation of NADPH and culminating in reduction of O2. Redox components in the multienzyme complex will be systematically characterized in terms of their association with one another and their overall role in effecting superoxide formation through oxidation of NADPH. In particular, the linkage of NADPH dependent quinone reductase activity with a b ty pe cytochrome, both recently discovered components of the oxidoreductase complex, will be examined by immu nochemical and reconstitution studies to clarify how these two components effect superoxide formation. The chemical identity of the native substrate of the quinone reductase will be sought, and enzymatic tests for intrinsic quinol dehydrogenase activity, a fourth postulated component of the oxidoreductase complex, will also be conducted on subcellular fractions derived from stimulated PMN's rich in oxidoreductase activity. A major effort will be devoted toward purifying the oxidoreductase complex from crude subcellular fractions in the belief that this approach will facilitate ch aracterization of its multi-enzyme structure. Long range goals are to define the enzymology and mechanism by which the oxidoreductase complex effects superoxide production. This should lead to a better understanding of how phagocytes effect bacterial killing, and may clarify how inappropriate activation precipitates acquisition of certain degenerative and autoimmune disorders. In addition, characterization may lead to the development of new active site titrants which may serve as anti-inflammatory agents directed against the oxidoreductase. The application of these active site titrants as anti-inflammatory agents may eliminate many of the adverse side effects commonly experienced with present-day, non-specific anti-inflammatory agents.